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Frontiers in Clinical Drug Research - Anti-Infectives最新文献

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Nanoantibiotics: Recent Developments and Future Prospects 纳米抗生素:最新发展和未来展望
Pub Date : 2019-06-10 DOI: 10.2174/9781681086378119050006
M. Ovais, N. Zia, A. Khalil, M. Ayaz, Amjad Khalil, Irshad Ahmad
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引用次数: 25
Therapeutic Use of Commensal Microbes: Fecal/Gut Microbiota Transplantation 共生微生物的治疗应用:粪便/肠道菌群移植
Pub Date : 2019-06-10 DOI: 10.2174/9781681086378119050004
P. A. Vanny, Aline Machiavelli, Catherine W. Wippel, Jessica Rodrigues de Andrade, C. P. Zamparette, D. C. Tartari, T. Sincero, A. R. Pinto, C. Zárate-Bladés
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引用次数: 2
Alternative Approaches to Antimicrobials 抗微生物药物的替代方法
Pub Date : 2019-06-10 DOI: 10.2174/9781681086378119050005
A. Filazi, B. Yurdakok-Dikmen
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引用次数: 0
Targeting Magnesium Homeostasis as Potential Anti-infective Strategy Against Mycobacteria 靶向镁稳态作为潜在的抗分枝杆菌感染策略
Pub Date : 2019-06-10 DOI: 10.2174/9781681086378119050008
S. Hameed, Z. Fatima
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引用次数: 0
List of Contributors 贡献者名单
Pub Date : 2019-06-10 DOI: 10.2174/9781681086378119050002
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引用次数: 0
Cranberry Juice and Other Functional Foods in Urinary Tract Infections in Women: A Review of Actual Evidence and Main Challenges 蔓越莓汁和其他功能食品对女性尿路感染的影响:实际证据和主要挑战的综述
Pub Date : 2019-06-10 DOI: 10.2174/9781681086378119050007
R. Monroy-Torres, Ana Karen Medina-Jiménez
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引用次数: 1
Frontiers in Clinical Drug Research - Anti-Infectives: Volume 5 临床药物研究前沿-抗感染:第5卷
Pub Date : 2017-11-16 DOI: 10.2174/97816810863781190501
Atta-ur- Rahman
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引用次数: 0
Integrated Approaches for Marine Actinomycete Biodiscovery 海洋放线菌生物发现的综合方法
Pub Date : 2017-09-01 DOI: 10.2174/9781681086378119050003
Larissa Buedenbender
This PhD project examined integrated approaches for marine actinomycete biodiscovery. A library of 120 actinomycete strains derived from the three Australian ascidians, Symplegma rubra, Aplidium solidium and Polyclinum vasculosum, was established in order to access new chemical diversity of underexplored marine ecological niches for natural product drug discovery. Specifically, the genera Streptomyces and Micromonospora were highly diverse and abundantly present, while fewer Nocardia and Rhodococcus and only one Streptosporangium representative were isolated. Only two isolates occurred in all three ascidians indicating speciesspecificity of actinomycetes in the ascidian. LC-MS/MS profiling of extracts obtained from the ascidians and their actinomycete associates revealed many overlapping ions between hosts and cultured isolates indicating that these compounds were likely to be synthesised by the microbial associates. Laboratory cultures of the actinomycetes displayed even more diverse metabolomes than those of their ascidian hosts; thus making ascidian-associated actinomycetes an excellent target for biodiscovery. Reisolation of already known compounds is a major obstacle to natural product drug discovery; therefore, sophisticated dereplication approaches have to be employed in the early stages of discovery. To facilitate the dereplication, a new strain prioritisation approach using HSQC-TOCSY NMR spectra together with anti-plasmodial activity data was developed. This allowed for prioritisation of microbial strains that are more likely to produce diverse polyketide or peptide natural products. This approach was further validated through dereplication of monoand co-culture extracts of four different microbial strains. HSQC-TOCSY NMR profiles of the extracts clearly showed co-cultivation induced changes in the microbial metabolomes. Streptomyces sp. (USC-16018) was selected based on the strain prioritisation approach and large-scale fermentations led to the isolation of a new ansamycin polyketide, herbimycin G with weak anti-plasmodial activity (77 % at 40 μM), as well as the known compounds elaiophylin, and the four diketiopiperazines, Cyclo-L-Pro-L-Leu, Cyclo-L-Pro-L-Phe, Cyclo-L-Pro-L-Val and Cyclo-L-Pro-L-Tyr. The crude NMR profile of the sediment-derived Streptomyces sp. (USC- 636) revealed the presence of indole-associated signals and three tryptophan containing diketopiperazines, naseseazine A – C, were isolated. The new compound naseseazine C exhibited moderate anti-plasmodial activity (IC50 3.52 μM). Overall, this thesis highlights the immense chemical diversity of actinomycetes from marine sources, as well as the importance of sophisticated dereplication approaches and provides an alternative new solution for strain selection that has led to the discovery of new bioactive natural products with potential as new drug leads.
本博士课题研究海洋放线菌生物发现的综合方法。摘要建立了120株来自澳大利亚海鞘(simplegma rubra、Aplidium solidum和Polyclinum vascullosum)的放线菌文库,以获取尚未开发的海洋生态位的新化学多样性,用于天然产物药物的开发。其中链霉菌属和小单孢菌属种类丰富,诺卡菌属和红球菌属较少,链孢菌属仅一种。在所有三种海鞘中仅出现两株分离株,表明海鞘中放线菌具有种特异性。从海鞘及其放线菌伴生物提取的LC-MS/MS分析显示,在宿主和培养的分离物之间有许多重叠的离子,表明这些化合物可能是由微生物伴生物合成的。放线菌的实验室培养比它们的海鞘宿主显示出更多样化的代谢组;因此,海鞘相关放线菌是生物发现的一个极好的目标。重新分离已知化合物是天然产物药物发现的主要障碍;因此,必须在发现的早期阶段采用复杂的反复制方法。为了方便重复,开发了一种新的菌株优先排序方法,使用HSQC-TOCSY核磁共振光谱和抗疟原虫活性数据。这允许微生物菌株的优先级,更有可能产生多种聚酮或肽天然产物。通过四种不同微生物菌株的单培养和共培养提取物的分离,进一步验证了该方法的有效性。提取物的HSQC-TOCSY NMR谱清楚地显示了共同培养诱导的微生物代谢组的变化。根据菌株优先级筛选方法筛选出Streptomyces sp. (USC-16018),并通过大规模发酵分离到一种新的抗疟原虫活性较弱的多酮类化合物herbimycin G(在40 μM下抗疟原虫活性为77%),以及已知化合物elaiophylin和四种双酮哌唑类化合物cyclol - pro - l - leu、cyclol - pro - l - phe、cyclol - pro - l - val和cyclol - pro - l - l - tyr。沉积物源Streptomyces sp. (USC- 636)的粗核磁共振谱显示存在吲哚相关信号,并分离到三种含色氨酸的二酮哌嗪,naseseazine A - C。新化合物naseseazine C具有中等的抗疟原虫活性(IC50为3.52 μM)。总体而言,本论文强调了海洋放线菌的巨大化学多样性,以及复杂的去复制方法的重要性,并为菌株选择提供了另一种新的解决方案,该解决方案导致发现新的生物活性天然产物,具有潜在的新药先导。
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引用次数: 3
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Frontiers in Clinical Drug Research - Anti-Infectives
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